The cellular and molecular mechanisms involved in gingivitis and periodontitis will be studied using a concerted biochemical, pharmacological and cell biological approach. These are the two major periodontal diseases and affect virtually the entire population to some degree. Both conditions are characterized by inflammation; periodontitis also involves bone resorption. Thus, regulation of the cellular components of the inflammatory response and their effect on the metabolism of bone plays a key role in periodontal disease. Accumulating data, both in vivo and in vitro, strongly suggests that heparin plays a critical role in the vessel wall as a regulator of smooth muscle cell growth. Heparin has also been shown to increase the amount of bone resorbed in cultured bone explants. The exact mechanism by which heparin functions in regulating smooth muscle cell growth and bone resorption are not known. Based on preliminary experiments, the effect of heparin on the synthesis of specific proteins thought to be important in the regulation of cell growth will be biochemically characterized and their functional significance analyzed. The specificity and structure-function relationships of the heparin effect on bone resorption will be determined and compared to the antiproliferative and anticoagulant properties of heparin. The activity of antiproliferative heparin-like species produced by endothelial cells will be examined in the bone resorption process. Experiments are also designed to analyze the effect of heparin on bone resorption process and include: alterations in the synthesis of proteins, the production of factors that induce chemotaxis, and the presence or production of molecules that specifically interact with heparin.
